Project Summary In this application we propose to develop the endoscopic ultrasound fine-needle optical diagnostic system that can determine the cellular composition of pancreatic cysts in vivo and identify cystic lesions with early stage cancer features. Pancreatic cancer is the 3rd leading cause of cancer-related death in the United States, surpassing breast cancer. With a median survival of 3 months, it has the highest mortality rate of all major cancers. The poor prognosis of pancreatic cancer is due in large part to the inability to detect this cancer at an early stage, when the option of a curative surgical resection is still possible. It is estimated that 8 million Americans have pancreatic cystic lesions. Pancreatic cysts are the only readily identifiable precursors of pancreatic cancer. Most commonly, these asymptomatic cysts are found incidentally when MRI/CT imaging is performed for other purposes and then monitored with these imaging techniques for interval growth since about 1 in 10 cysts have malignant potential. While CT and MRI could be used to screen for cystic lesions, they have poor accuracy with regard to distinguishing cancerous and pre-cancerous cysts from benign cysts. Currently, there is no accurate diagnostic technique that can distinguish cancerous and pre-cancerous cysts from benign cysts, resulting in dire consequences, including the development of cancer in cysts thought to be benign, or unnecessary pancreatic surgery for benign cysts, often with significant morbidity and mortality. Thus, there is a critical need for a new diagnostic approach that accurately identifies those pancreatic cysts that require surgical intervention and those that do not. Recently we introduced a new diagnostic technology based on light scattering spectroscopy (LSS) that identifies the malignant potential of pancreatic cystic lesions during routine diagnostic minimally invasive endoscopic ultrasound-guided fine needle aspiration (EUS- FNA) procedures. It employs a single-point forward looking spatial gating contact probe that fits into a standard aspiration needle and samples a fraction of the internal surface of the cyst forward hemisphere in approximately 2 minutes. To improve accuracy and ensure clinical acceptance of the technique, scanning the entire internal cyst surface in a shorter time would be a significant advance. Our preliminary results are very encouraging, indicating that the proposed technology could be a tremendous aid in identifying both precursor lesions and early stage pancreatic cancers.